Characterizing the Behavior Profile of Healthy Cognitive Aging

表征健康认知衰老的行为特征

• 批准号: 7910656
• 负责人: PATRICIA A BOYLE
• 金额: $ 24.35万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910656
• 关键词: Accounting; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Autopsy; Behavior; Brain; Cerebral Infarction; Cerebrum; Cessation of life; Clinical; Cognition; Cognitive; Cognitive aging; Complement; Data; Data Set; Dementia; Disease; Elderly; Epidemiologic Studies; Epidemiology; Episodic memory; Evaluation; Exclusion; Exhibits; Funding; Goals; Impaired cognition; Infarction; Intervention; Knowledge; Lewy Bodies; Lewy Body Disease; Measurable; Measures; Memory; Modeling; Participant; Pathologic; Pathologic Processes; Pathology; Persons; Prevention; Prevention strategy; Public Health; Religion and Spirituality; Semantic memory; Short-Term Memory; Speed; Terminal Disease; Testing; Time; Visuospatial; age related cognitive change; base; cognitive change; cognitive function; cohort; effective therapy; follow-up; innovation; neuroimaging; neuropathology; novel; prevent; public health relevance

DESCRIPTION (provided by applicant): Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. Despite considerable progress in identifying the causes of cognitive decline in older persons, surprisingly little is known about the profile of healthy cognitive aging. Most of the available studies of healthy cognitive aging have examined cognitive change in persons without clinical dementia. However, the vast majority of persons without dementia who come to autopsy have extensive neuropathologic evidence of the diseases commonly known to cause cognitive impairment in old age, particularly Alzheimer's disease, cerebral infarcts, and Lewy bodies, and the exclusion of persons without clinical dementia does not account for the effect of accumulating neuropathology on the trajectory of cognitive aging. Moreover, most older persons exhibit a precipitous decline in cognition in the years just prior to death, a phenomenon referred to as terminal decline, and this also contributes to cognitive aging. Thus, a substantial portion of the cognitive decline currently attributed to healthy cognitive aging likely is due to the influence of accumulating neuropathology and terminal decline. We propose to use innovative statistical approaches to characterize the profile of healthy cognitive aging defined as age-related cognitive change not accounted for by the presence of common neuropathologies (i.e., Alzheimer's disease, cerebral infarcts, and the Lewy body diseases) or terminal decline. The proposed study will capitalize on the unique longitudinal cognitive and neuropathologic data available from two ongoing epidemiologic studies, the Religious Orders Study (P30AG10161), which will serve as the exploratory cohort, and the Rush Memory and Aging Project (R01AG17917), which will serve as the confirmatory cohort. These studies perform comparable and detailed annual cognitive evaluations on more than 2,300 persons in total, all of whom have agreed to brain donation. By the end of the funding period of the proposed study, more than 23,000 cognitive data points will be available from more than 2,500 persons with up to 20 years of annual follow-up. In addition, detailed post-mortem data will be available from more than 1,200 persons. Data from these studies will be used to model the trajectory of cognitive change as a function of accumulating neuropathology and terminal decline in order to elucidate the trajectory of healthy cognitive aging (i.e., age-related cognitive change not accounted for by common neuropathologies or terminal decline). The proposed study offers a novel, timely, and potentially powerful approach to identify the profile of healthy cognitive aging. Knowledge of the trajectory of healthy cognitive aging is essential for the identification of persons who might benefit from interventions to prevent age-related cognitive decline and, ultimately, for the identification of factors associated with successful aging. PUBLIC HEALTH RELEVANCE: Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. First, knowledge of the profile of healthy cognitive aging will allow for identification of persons exhibiting the earliest signs of pathologic cognitive aging who are most likely to benefit from the available therapies and disease modifying agents as they become available. Second, the proposed study will elucidate the extent to which common neuropathologies underlie age-related cognitive change and will directly inform on the public health burden associated with the diseases commonly known to cause cognitive impairment in old age; if common neuropathologies account for most of cognitive change seen in older persons, then these data would suggest that the public health burden posed by these diseases is greater than currently recognized and that a much larger group of persons, including those without overt dementia, ultimately may benefit from effective treatment and prevention strategies developed for cognitive impairment and dementia.

描述（由申请人提供）：老年人的认知下降几乎是普遍的，预防是21世纪最重要的公共卫生挑战之一。尽管在确定老年人认知能力下降的原因方面取得了很大进展，但令人惊讶的是，人们对健康认知衰老的概况知之甚少。健康认知衰老的大多数可用研究都检查了没有临床痴呆的人的认知变化。但是，大多数没有痴呆症的人都有广泛的神经病理学证据，表明人们通常已知会导致老年认知障碍，尤其是阿尔茨海默氏病，大脑梗死，刘易身体，刘基身体，刘基身体，以及没有临床痴呆症的人的排除在没有临床痴呆症的情况下，对累积的效应却不认为是累积的效应。此外，大多数老年人在死亡前几年表现出认知的急剧下降，这种现象称为终极下降，这也导致认知衰老。因此，当前归因于健康认知衰老的认知下降的很大一部分可能是由于累积神经病理学和最终下降的影响。我们建议使用创新的统计方法来表征健康认知衰老的概况定义为与年龄相关的认知变化，而不是存在常见的神经病理学（即阿尔茨海默氏病，大脑梗塞，脑梗死以及刘易体内疾病）或终止下降所无法解释的。拟议的研究将利用从两项正在进行的流行病学研究，宗教秩序研究（P30AG10161）获得的独特纵向认知和神经病理学数据，该研究将作为探索性记忆和衰老项目（R01AG17917），这将用作探索性人群，这将作为确认的人群。这些研究对总共2300多人进行了可比较和详细的年度认知评估，所有这些人都同意大脑捐赠。到拟议研究的资助期结束时，将有23,000多个认知数据点可从2500多人提供20年的年度随访。此外，将有1,200多人获得详细的验尸数据。这些研究的数据将用于对认知变化的轨迹进行建模，这是累积神经病理学和终末下降的函数，以阐明健康认知衰老的轨迹（即，常见的神经病理学或终末衰落无法解释与年龄相关的认知变化）。拟议的研究提供了一种新颖，及时且潜在的强大方法，以识别健康认知衰老的特征。了解健康认知衰老轨迹的知识对于鉴定可能受益于干预措施以防止年龄相关的认知能力下降的人至关重要，最终对于确定与成功衰老有关的因素。 公共卫生相关性：老年人的认知能力下降几乎是普遍的，预防是21世纪最重要的公共卫生挑战之一。首先，了解健康认知衰老的知识将允许鉴定出表现出最早的病理性认知衰老迹象的人，这些人最有可能从可用的疗法和疾病中受益，并在可用的情况下受益。其次，拟议的研究将阐明与年龄相关的认知变化构成基础的常见神经病理的程度，并将直接告知与常见的疾病相关的公共卫生负担。如果常见的神经病理学解释了老年人中的大部分认知变化，那么这些数据将表明，这些疾病所带来的公共卫生负担大于当前认可的公共卫生负担，并且包括没有明显痴呆的人在内的一群人，最终可能会受益于有效的治疗和预防策略，这些策略用于认知障碍和痴呆症。